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Utero Exposure (utero + exposure)
Selected AbstractsEffects of Subchronic versus Acute in utero Exposure to Dexmedetomidine on Foetal Developments in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2008Mohammad Tariq This study was undertaken to investigate the effects of in utero exposure of dexmedetomidine on foetal development and postnatal behaviour in the offspring. Pregnant Sprague-Dawley rats were chronically treated with dexmedetomidine (0, 5, 10 and 20 µg/kg, subcutaneously) daily from gestation day 7 to day 19. Another group of animals received only a single acute dose of dexmedetomidine (20 µg/kg) on gestational day 19 to mimic a model for systemic analgesia during labour. Administration of dexmedetomidine did not affect the frequency of implantations. Chronic administration of 10 and 20 µg/kg of dexmedetomidine significantly reduced the body weight and crown-rump length of pups, whereas a single acute dose (20 µg/kg) did not affect these parameters. None of the pups exhibited any external malformations or skeletal abnormalities irrespective of treatment assigned. All the pups showed a normal postnatal weight gain during the developmental phase. No significant differences were observed among any of the groups with respect to behavioural performances of offspring in beam balance, grip strength and inclined plane tests as well as motor activity. In conclusion, acute exposure to dexmedetomidine at the anticipated delivery time does not exert any adverse effects on perinatal morphology of pups, their birth weight, crown-rump length, physical growth and postnatal behavioural performances. Since this study was conducted in rats, its clinical relevance in human beings remains to be unclear and warrants further studies. [source] Effects of in utero exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153) on somatic growth and endocrine status in rat offspringCONGENITAL ANOMALIES, Issue 4 2008Kenichi Kobayashi ABSTRACT Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153), a di- ortho -substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose,anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153,treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153,treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10,16, 16,64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters. [source] Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of human lymphoblastoid cells or in utero exposure of CD-1 mice to single agents or drug combinations,,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3-4 2007Salina M. Torres Abstract Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using cell cloning assays for assessing the effects of individual drugs/drug combinations in (1) TK6 human lymphoblastoid cells exposed in vitro and (2) splenic lymphocytes from male CD-1 mice exposed transplacentally on days 12,18 of gestation. In TK6 cells, dose-related increases in HPRT and TK mutant frequencies were found following 3 days of exposure to AZT or 3TC alone (33, 100, or 300 ,M), or to equimolar amounts of AZT-3TC. Compared with single drug exposures, AZT-3TC coexposures generally yielded enhanced elevations in HPRT and TK mutant frequencies. Mutagenicity experiments with ABC alone, or in combination with AZT-3TC, were complicated by the extreme cytotoxicity of ABC. Exposure of cells either to relatively high levels of AZT-3TC short-term (100 ,M, 3 days), or to peak plasma-equivalent levels of AZT-3TC for an extended period (10 ,M, 30 days), resulted in similar drug-induced mutagenic responses. Among sets of mice necropsied on days 13, 15, or 21 postpartum, Hprt mutant frequencies in T-cells were significantly elevated in the AZT-only (200 mg/kg bw/day) and AZT-3TC (200 mg AZT + 100 mg 3TC/kg bw/day) groups at 13 days of age. These results suggest that the mutagenicity by these nucleoside analogs is driven by cumulative dose, and raises the question of whether AZT-3TC has greater mutagenic effects than AZT alone in perinatally exposed children. Environ. Mol. Mutagen. © 2007 Wiley-Liss, Inc. [source] Topical dose delivery in the reptilian egg treatment modelENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2007Jennifer K. Muller Abstract Developing assays to detect endocrine-mediated toxicity from in ovo or in utero exposure is a current challenge in regulatory toxicology. Some species of reptiles exhibiting a unique mode of sex determination, in which the incubation temperature during a critical period determines gonadal sex, have been explored as an in ovo model to screen environmental contaminants for endocrine effects. We critically review published egg-exposure studies and conclude that data regarding the pharmacokinetics of topically applied substances are insufficient to validate dose,response relationships for the effects of chemicals on in ovo endocrine function or gender determination in reptiles. The insufficiencies in these data largely result from methodological failures, including lack of measurement verification, failure to investigate and control extraneous factors affecting the measurements, and lack of independent replication of results. Considerable additional research will be necessary to alleviate these methodological inadequacies. Given the current status of the data, topical treatment of reptilian eggs cannot be considered to be a valid means of establishing causal relationships between chemical treatment and biological outcome. [source] Role of cortical dysplasia in epileptogenesis following prolonged febrile seizureEPILEPSIA, Issue 9 2010Kyung-Il Park Summary Purpose:, Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model. Methods:, Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM-treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long-term video-EEG (electroencephalography). Results:, The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC-only and MAM-only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group. Discussion:, Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE. [source] In utero exposure to vigabatrin: No indication of visual field lossEPILEPSIA, Issue 2 2009Charlotte Lawthom Summary The purpose of the study was to determine whether in utero exposure to vigabatrin caused visual field loss. Three mothers with four children who had been exposed to vigabatrin in utero and who were subsequently formula fed were identified. All seven individuals underwent perimetry and imaging of the retinal nerve fiber layer (RNFL). All individuals yielded reliable outcomes to perimetry and RNFL images of acceptable quality. Two of the three mothers exhibited vigabatrin-attributed visual field loss and an abnormally attenuated RNFL. The third exhibited an upper left quadrantanopia, consistent with previous temporal lobe surgery, and a normal RNFL. All four children yielded normal visual fields and RNFL thicknesses. The presence of the normal findings for the children is reassuring and, if representative, suggests a lack of vigabatrin visual toxicity and therefore obviates the need for ophthalmological examination of those exposed to vigabatrin prenatally. [source] Ocular complications of neurological therapyEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2005S. Hadjikoutis Treatments used for several neurological conditions may adversely affect the eye. Vigabatrin-related retinal toxicity leads to a visual field defect. Optic neuropathy may result from ethambutol and isoniazid, and from radiation therapy. Posterior subcapsular cataract is associated with systemic corticosteroids. Transient refractive error changes may follow treatment with acetazolamide or topiramate, and corneal deposits and keratitis with amandatine. Intraocular pressure can be elevated in susceptible individuals by anticholinergic drugs, including oxybutynin, tolterodine, benzhexol, propantheline, atropine and amitriptyline, and also by systemic corticosteroids and by topiramate. Nystagmus, diplopia and extraocular muscle palsies can occur with antiepileptic drugs, particularly phenytoin and carbamazepine. Ocular neuromyotonia can follow parasellar radiation. Congenital ocular malformations can result from in utero exposure to maternally prescribed sodium valproate, phenytoin and carbamazepine. Neurologists must be aware of potential ocular toxicity of these drugs, and appropriately monitor for potential adverse events. [source] Reproductive function in male rats after brief in utero exposure to diethylstilboestrolINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2000G. H. G. Behrens Long-term effects of brief in utero exposure to diethylstilboestrol (DES) during a foetal period known to be critical for gonadal development were evaluated. Rats were exposed to DES (100 ,g/kg body-weight) from day 17 to 19 of pregnancy. All of the DES-treated pregnant rats (11/11) ate parts or whole of their offspring during the first day after birth (p=0.03). Surviving male offspring were examined on day 63 post-partum. DES induced a reduction in weight of the testis (p=0.06) and ventral prostate (p=0.07), even after this short exposure. DES tended to reduce the number of Sertoli cells (p=0.13). Our findings indicate that even a short in utero exposure of rats to DES during a critical period for gonadal development results in cannibalism and reduced testis and ventral prostate weight. [source] Effect of lindane on CYP-mediated steroid hormone metabolism in male mice following in utero exposureJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2009Emma Di Consiglio Abstract A wide number of pesticides, including highly persistent organochlorinated compounds, such as lindane (LIN), may induce reproductive and developmental alterations by directly binding to the estrogen/androgen receptors or altering steroid hormone metabolism. In the present work, we have investigated whether LIN in utero exposure of CD1 mice affects the reproductive system in male offspring by causing an impairment of the CYP-dependent steroid hormone metabolism. Dam exposure to 25 mg kg,1 b.w. LIN occurred during critical developmental periods, from gestational days 9 to 16. Effects on hepatic CYP-mediated testosterone (TST) hydroxylase, aromatase activities and testicular parameters were tested at postnatal days (PND 50, 65,69, 100) that are critical for sexual maturation in CD1 mice. In the adult F1 mice significant changes of male reproductive endpoints (testis weight, spermatid number) as well as dramatic effects on CYP-mediated TST metabolism were observed on PND 65,69, in the absence of any of systemic toxicity. The levels of TST 6, - and 2, -hydroxylation and dehydrogenation showed the highest level of reduction, suggesting CYP 3A and 2C families as the major target of LIN induced effects. All changes were almost recovered on PND 100. No effects on aromatase activity were evidenced. Overall, these findings provide useful information for a better characterization of the LIN mode of action. They suggest that LIN-induced toxicity in males is linked to an impairment of steroid hormone homeostasis, due to CYP-mediated TST catabolism modulation and differs from LIN receptor-mediated mechanism previously reported in females. Copyright © 2009 John Wiley & Sons, Ltd. [source] Differential developmental toxicities of di- n -hexyl phthalate and dicyclohexyl phthalate administered orally to ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2009Anne-Marie Saillenfait Abstract The objective of this study was to evaluate the developmental toxic potential of di- n -hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague,Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg,1 per day, by gavage, on gestational days (GD) 6,20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg,1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including marked embryo mortality at 750 mg kg,1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg,1 per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg,1 per day. DCHP produced fetal growth retardation at 750 mg kg,1 per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg,1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP. Copyright © 2009 John Wiley & Sons, Ltd. [source] Inorganic arsenic as a developmental toxicant: In utero exposure and alterations in the developing rat lungsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2009Jay S. Petrick Abstract In the present study, we characterize the toxic effects of in utero arsenic exposure on the developing lung. We hypothesize that in utero exposure to inorganic arsenic through maternal drinking water causes altered gene and protein expression in the developing lung, indicative of downstream molecular and functional changes. From conception to embryonic day 18, we exposed pregnant Sprague-Dawley rats to 500 ppb arsenic (as arsenite) via the drinking water. Subtracted cDNA libraries comparing control to arsenic exposed embryonic lungs were generated. In addition, a broad Western blot analysis was performed to identify altered protein expression. A total of 59 genes and 34 proteins were identified as being altered. Pathway mapping and analysis showed that cell motility was the process most affected. The most likely affected pathway was alteration in integrin signaling through the ,-catenin pathway, altering c-myc. The present study shows that arsenic induces alterations in the developing lung. These data may be useful in the elucidation of molecular targets and biomarkers of arsenic exposure during lung development and may aid in understanding the etiology of arsenic induced adult respiratory disease and lung cancers. [source] Craniofacial skeletal deviations following in utero exposure to the anticonvulsant phenytoin: monotherapy and polytherapyORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 1 2003HI Orup Jr Structured Abstract Authors , Orup Jr HI, Holmes LB, Keith DA, Coull BA. Objective , To identify and quantify the craniofacial effects from prenatal exposure to phenytoin monotherapy and polytherapy using cephalometric, hand-wrist, and panoramic radiographs and to determine if such deviations persist with age. Design , Craniofacial structures of 28 anticonvulsant-exposed individuals were evaluated using 20 landmarks in lateral cephalometric radiographs and 19 landmarks in frontal cephalometric radiographs. Skeletal maturity was assessed using hand-wrist radiographs. Dental maturity and the presence of dental anomalies were evaluated using panoramic radiographs. Eleven individuals were re-evaluated 7 years later, on average, to determine the persistence of any measured deviations. Setting and Sample Population , Department of Growth and Development, Harvard School of Dental Medicine and Massachusetts General Hospital. Patients were recruited from several sources. Outcome Measure , The evaluated dimensions included linear, angular, and proportional measures. Results , The most common deviations were decreased height and length of the maxilla, decreased length of the posterior cranial base, length of the mandible, cranial width and level of the cribriform plate, and a decrease in the Wits Appraisal assessment. The deviations were more significant in the polytherapy-exposed individuals than in the monotherapy-exposed individuals. These deviations, especially in the maxilla, persisted with age as revealed in a re-evaluation of 11 individuals. Conclusion , The craniofacial skeletal findings among individuals exposed in utero to phenytoin monotherapy or phenytoin polytherapy, when considered in aggregate, suggest a mild pattern of maxillary hypoplasia that becomes more pronounced with age. [source] Primary mucinous adenocarcinoma of the vagina: Possibility of differentiating from metastatic adenocarcinomasPATHOLOGY INTERNATIONAL, Issue 6 2005Maki Saitoh Primary vaginal adenocarcinomas are rare neoplasms. Herein is reported a case of primary vaginal mucinous adenocarcinoma with an interesting mucin profile, presumably arising from a lesion of adenosis in a patient without in utero exposure to diethylstilbesterol (DES). The patient, a 44-year-old woman, had undergone vaginal total hysterectomy 10 years previously for myoma uteri corporis. The histological features of the vaginal intramural tumor found in this patient resembled those of mucinous adenocarcinoma of the endocervical type. Therefore, it was necessary to determine whether or not the tumor was metastatic from an occult cervical adenocarcinoma. However, the adenocarcinoma cells of the present case did not contain sulfomucin at all, being different from most mucinous adenocarcinoma cells of the endocervical type. Moreover, there were foci of adenosis adjacent to the adenocarcinoma foci, which also did not contain sulfomucin. These findings indicate that the mucinous adenocarcinoma arose from vaginal adenosis. Further studies are necessary to investigate whether lack of sulfomucin expression is a characteristic feature of vaginal adenosis. [source] Epidemiology of childhood type 2 diabetes and obesityPEDIATRIC DIABETES, Issue 2007Jonathan Shaw Abstract:, Over the last decade, it has become apparent that type 2 diabetes extends not only into the young adult population but is also found in adolescents and even, occasionally, in children. The limited data that are currently available present a rather uncertain picture, with a rather wide range of prevalences and incidences of type 2 diabetes in children and adolescents. Not surprisingly, the majority of the cases, and the highest prevalences, have been found among ethnic groups known to be at high risk of adult type 2 diabetes. Nevertheless, even in European populations, where the prevalence of type 2 diabetes remains very low among children and adolescents and certainly is considerably smaller than type 1 diabetes, there are several cases reported. The risk factors for type 2 diabetes in children and adolescents are, as expected, similar to those seen in adults, with obesity being almost always present. In utero exposure to hyperglycemia now appears to be an additional risk factor to having a family history of diabetes and suggests that better management of diabetes in pregnancy and prevention of gestational diabetes may reduce the risk of diabetes developing in the offspring. [source] Antiproliferative effect of Scutellaria barbata D. Don. on cultured human uterine leiomyoma cells by down-regulation of the expression of Bcl-2 proteinPHYTOTHERAPY RESEARCH, Issue 5 2008Kyung-Woon Kim Abstract Scutellaria barbata D. Don (Lamiaceae; SB) inhibited the growth of leiomyomal cells (LM). A time-dependent antiproliferative effect was noted when 10,5m buserelin, gonadotrophin-releasing hormone (GnRH) agonist or 20,40 µg/mL SB was added. The inhibition of cell growth decreased with the addition of the PKC activator (12-O-tetradecanoylphorbor-13-acetate; TPA) much as it did with the addition of SB, and the decreases in the viable cells caused by the addition of SB were reversed completely by pretreatment with a protein kinase C (PKC) inhibitor (calphostin C). The findings suggest that SB inhibits cell proliferation in cultured human uterine leiomyoma cells accompanied by PKC activation. Next, the study investigated the effect of SB on fetal development for toxicity. Pregnant Sprague-Dawley rats, from gestation day 6,15, were administered 20 g/L or 50 g/L SB in the drinking water and then killed on day 20. No maternal toxicity was observed, however, embryonic loss in the treatment groups was double that of the controls (p < 0.05). No gross morphologic malformations were seen in the treated fetuses. Fetuses exposed to SB were found to be significantly heavier than the controls, an effect that was greater in female fetuses and was not correlated with increased placental size. The results suggest that the SB had no toxicity and that in utero exposure to SB resulted in increased early embryo loss with increased growth in surviving fetuses. On the other hand, Western blot analyses revealed that Bcl-2 protein of a 26 kDa was abundant in leiomyomal cells, but not in normal myometrial cells. The addition of progesterone (100 ng/mL) resulted in a striking increase in Bcl-2 protein expression in the cultured leiomyoma cells. However, the addition of SB (20 µg/mL) resulted in a significant reduction in Bcl-2 protein expression in the cells. The results indicated that human uterine leiomyomal cells express Bcl-2 protein and progesterone enhances its expression, however, SB reduces the expression of Bcl-2 protein in human uterine leiomyoma cells. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effects of Subchronic versus Acute in utero Exposure to Dexmedetomidine on Foetal Developments in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2008Mohammad Tariq This study was undertaken to investigate the effects of in utero exposure of dexmedetomidine on foetal development and postnatal behaviour in the offspring. Pregnant Sprague-Dawley rats were chronically treated with dexmedetomidine (0, 5, 10 and 20 µg/kg, subcutaneously) daily from gestation day 7 to day 19. Another group of animals received only a single acute dose of dexmedetomidine (20 µg/kg) on gestational day 19 to mimic a model for systemic analgesia during labour. Administration of dexmedetomidine did not affect the frequency of implantations. Chronic administration of 10 and 20 µg/kg of dexmedetomidine significantly reduced the body weight and crown-rump length of pups, whereas a single acute dose (20 µg/kg) did not affect these parameters. None of the pups exhibited any external malformations or skeletal abnormalities irrespective of treatment assigned. All the pups showed a normal postnatal weight gain during the developmental phase. No significant differences were observed among any of the groups with respect to behavioural performances of offspring in beam balance, grip strength and inclined plane tests as well as motor activity. In conclusion, acute exposure to dexmedetomidine at the anticipated delivery time does not exert any adverse effects on perinatal morphology of pups, their birth weight, crown-rump length, physical growth and postnatal behavioural performances. Since this study was conducted in rats, its clinical relevance in human beings remains to be unclear and warrants further studies. [source] Chemical-induced, nonlethal, developmental model of dissecting aortic aneurysm,BIRTH DEFECTS RESEARCH, Issue 1 2006Bin Gong BACKGROUND A chemical-induced, nonlethal, dissecting aortic aneurysm (DAA) is described following in utero exposure to semicarbazide, an inhibitor of the vascular enzyme semicarbazide sensitive amine oxidase (SSAO). METHODS Sprague-Dawley rat dams were given semicarbazide (0.096,49.000 mg/kg/day) by IP injection on gestation days (GDs) 14,20, a period of rapid aortic development. Newborn rats (day 1) were killed and their thoracic organs were removed en bloc for near-serial cross sections and routine histopathology, Movat stain for elastin, and immunohistochemistry to differentiate cells involved in the evolution of the DAA. In subsequent experiments, pups from treated dams (0.096,6.125 mg/kg/day) were allowed to survive for 7 or 28 days. RESULTS DAA occurred in nearly 100% of the rats at all doses except the lowest tested (1.530, 0.096 mg/kg/day). Dissections frequently extended to the carotids and, less frequently, to the abdominal aorta. Remodeling of vascular lesions proceeded by organization of collections of blood in vascular media (the "false lumen"), proliferation of vascular smooth muscle cells, fibrosis, and formation of irregular frayed elastic lamellae in healed vascular media. Biochemical quantitation and Western blot analysis of main extracellular matrix proteins on GD 20 showed no overt difference in expression of collagen type I, fibrillin-1, or elastin. CONCLUSION This developmental model provides investigators an opportunity to explore the pathologic mechanisms of DAA and to examine the potential long-term effects of vascular remodeling of DAA. Birth Defects Research (Part A), 2005. © 2005 Wiley-Liss, Inc. [source] Defects in cervical vertebrae in boric acid-exposed rat embryos are associated with anterior shifts of hox gene expression domainsBIRTH DEFECTS RESEARCH, Issue 1 2003Nathalie Wéry BACKGROUND Previously, we showed that prenatal exposure to boric acid (BA), an industrial agent with large production, causes alterations of the axial skeleton in rat embryos, reminiscent of homeotic transformations. Indeed, Sprague-Dawley rats exposed in utero to BA on gestation day 9 (GD 9) had only six, rather than the normal seven, cervical vertebrae. This finding, observed in 91% of GD 21 fetuses, suggests posterior transformations of vertebrae. The present study attempts to determine if these skeletal alterations could be explained by modifications of the hox code, involved in the establishment of positional information along the craniocaudal axis of the embryo. METHODS Pregnant rats were treated by gavage with BA (500 mg/kg, twice) on GD 9. Embryos were collected on GD 11 or GD 13.5 and processed for in situ hybridization. Several hox genes were selected according to the position of their cranial limit of expression in the cervical and thoracic region. RESULTS At GD 13.5, we detected a cranial shift of the anterior limit of expression of hoxc6 and hoxa6. We observed no difference between control and treated embryos in the location of the cranial limit of expression of the other genes: hoxd4, hoxa4, hoxc5, and hoxa5. CONCLUSIONS Our results demonstrate that following in utero exposure to BA on GD 9, a disturbance of the expression of hox genes involved in the specification of most anterior vertebrae is observed at GD 13.5. Based on their expression domain and on their implication in the definition of the cervicothoracic vertebral boundary, it is likely that the anteriorization of hoxc6 and hoxa6 reported here is correlated to the morphological phenotype observed in BA-exposed fetuses at GD 21. Birth Defects Research (Part A) 67:59,67, 2003. © 2003 Wiley-Liss, Inc. [source] In utero exposure to female hormones and germ cell tumors in children,CANCER, Issue 5 2006M.P.H., Sadhna Shankar M.D. Abstract BACKGROUND Maternal exposure to exogenous female hormones during pregnancy has been implicated as a risk factor for malignant germ cell tumors (GCTs) in the offspring in some epidemiologic studies of testicular and ovarian carcinoma in adults. METHODS From 1996 to 2002, 278 children younger than 15 years of age with malignant GCTs and 423 healthy controls, frequency-matched for geographic location, age, and sex were enrolled in a case,control study to investigate whether in utero exposure to female hormones is associated with the risk of malignant GCT in children. Cases were recruited from 84 institutions in the U.S. and controls were enrolled through random digit dialing. Information was obtained through telephone interview with the biological mothers of the subjects and through blinded review of the mothers' medical records. RESULTS Neither self-reported (odds ratio [OR] = 1.15; 95% confidence interval [CI], 0.63, 2.12) nor medical chart based (OR = 1.14; 95% CI, 0.75, 1.73) maternal exposure to exogenous female hormones was related to malignant GCT risk. Pregnancy-related conditions that may have altered serum levels of circulating female hormones were also unrelated to the risk of GCT in the offspring. CONCLUSION This study failed to provide strong evidence to support the hypothesis that maternal exposure to exogenous female hormones during pregnancy increases the risk of GCT in the offspring. Cancer 2006. © 2006 American Cancer Society. [source] Thimerosal exposure (from tetanus-diphtheria vaccine) during pregnancy and neurodevelopment of breastfed infants at 6 monthsACTA PAEDIATRICA, Issue 6 2010RC Marques Abstract Aim:, We studied the effect on neurodevelopment of infants who are exposed to thimerosal in tetanus-diphtheria (Td) vaccines during pregnancy. Methods:, We compared Gesell Developmental Schedules (GDS) of exclusive breastfed infants at 6 months born to mothers who received Td (1 to 3 doses) against those who were born to mothers who did not take such vaccines. Results:, Compared with the group of infants not exposed to ethylmercury in utero, the infants of exposed mothers showed no significant difference in neurodevelopment delays. Although there was a significant correlation between hair-Hg of mothers and hair-Hg of neonates (Spearman r = 0.353; p = 0.0011), there was no significant correlation between the level of in utero exposure to ethylmercury in Td vaccines and neonate's hair-Hg concentrations (Spearman r = 0.060; p = 0.5922). However, regression analysis showed that GDS at 6 months was significantly associated with total mercury concentration of neonate's hair but was not sensitive to the number of vaccines taken by the mother. Conclusion:, Early neurodevelopment of exclusively breastfed infants is sensitive to in utero exposure to mercury, but maternal thimerosal exposure in tetanus-diphtheria vaccines per se cannot portend clinical neurodevelopment delays measured by GDS at 6 months. [source] Accelerated rejection following offspring-to-mother and husband-to-wife transplantsCLINICAL TRANSPLANTATION, Issue 6 2004Jerry C. Rosenberg Abstract:, It has been demonstrated that graft survival rates of offspring-to-mother and husband-to-wife renal transplants are equivalent to those of other living donors. Although the vast majority of these transplants proceed without incident, we have encountered several instances of delayed accelerated rejections that are not predicted by a positive cross-match. The accelerated rejection can result from an anamnestic reaction subsequent to the in utero exposure of the mother to human leukocyte antigen (HLA) antigens of the fetus with sensitization developing during the pregnancy. [source] | |||||||||||||||||||||||||